Variant 14-20994882-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000339374.11(METTL17):c.857G>A(p.Arg286His) variant causes a missense change. The variant allele was found at a frequency of 0.0000434 in 1,613,482 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

METTL17
ENST00000339374.11 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.74

Variant links:

Genes affected

METTL17 (HGNC:19280): (methyltransferase like 17) Predicted to enable S-adenosyl-L-methionine binding activity and mitochondrial ribosome binding activity. Predicted to be involved in ribosomal small subunit biogenesis. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

METTL17 links:

METTL17 (HGNC:):

METTL17 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
METTL17	NM_022734.3 linkuse as main transcript	c.857G>A	p.Arg286His	missense_variant	9/14	ENST00000339374.11	NP_073571.1	Q9H7H0-1A0A0S2Z5L8
METTL17	NM_001029991.2 linkuse as main transcript	c.857G>A	p.Arg286His	missense_variant	9/13		NP_001025162.1	Q9H7H0-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
METTL17	ENST00000339374.11 linkuse as main transcript	c.857G>A	p.Arg286His	missense_variant	9/14	1	NM_022734.3	ENSP00000343041.6		Q9H7H0-1

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000439

AC:

AN:

250516

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135348

show subpopulations

Gnomad AFR exome

AF:

0.000432

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000363

AC:

AN:

1461252

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

726874

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000306

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.000112

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.000386

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000433

Hom.:

Bravo

AF:

0.000121

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 18, 2021

The c.857G>A (p.R286H) alteration is located in exon 9 (coding exon 9) of the METTL17 gene. This alteration results from a G to A substitution at nucleotide position 857, causing the arginine (R) at amino acid position 286 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.090

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.031

T;.;.

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.95

D;D;D

M_CAP

Benign

0.022

MetaRNN

Uncertain

0.49

T;T;T

MetaSVM

Benign

-0.53

MutationAssessor

Uncertain

2.5

M;M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-2.4

N;D;.

REVEL

Benign

0.28

Sift

Benign

0.048

D;D;.

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.59

MVP

0.76

MPC

1.1

ClinPred

0.33

GERP RS

6.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.46

gMVP

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over